Rational design and application of responsive alpha-helical peptide hydrogels.
Rational design and application of responsive alpha-helical peptide hydrogels.
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生物相容性水凝胶在生物技术和医学中具有广泛的潜在应用，如细胞、化妆品和药物的控制递送和释放；作为细胞生长和组织工程的支持。合理的肽设计和工程正在成为这类功能性生物材料的有希望的新途径。在这里，我们提出了基于纯α-螺旋结构的标准线性肽的合理设计和完全表征的自组装水凝胶的第一个例子，我们称之为水凝胶自组装纤维（hSAFs）。这些形成了α-螺旋原纤维的跨越网络，相互作用形成了自支撑的物理水凝胶，含水量为100 - 99%。肽序列可以被改造来改变凝胶的潜在机制，从而改变水凝胶的性质。有趣的是，例如，那些有氢键网络的在加热时融化，而那些通过疏水相互作用形成的在加热时加强。hSAFs是双肽系统，只在混合时凝胶化，这对组装有严格的控制。这些特性增加了在细胞培养中使用hSAFs作为底物的可能性。我们已经将其与广泛使用的Matrigel底物进行了比较，并证明，与Matrigel一样，hsas支持大鼠肾上腺嗜铬细胞瘤细胞在培养中持续生长和分化。
Biocompatible hydrogels have a wide variety of potential applications in biotechnology and medicine, such as the controlled delivery and release of cells, cosmetics and drugs; and as supports for cell growth and tissue engineering. Rational peptide design and engineering are emerging as promising new routes to such functional biomaterials. Here we present the first examples of rationally designed and fully characterized self-assembling hydrogels based on standard linear peptides with purely α-helical structures, which we call hydrogelating self-assembling fibres (hSAFs). These form spanning networks of α-helical fibrils that interact to give self-supporting physical hydrogels of >99% water content. The peptide sequences can be engineered to alter the underlying mechanism of gelation and, consequently, the hydrogel properties. Interestingly, for example, those with hydrogen-bonded networks melt upon heating, whereas those formed via hydrophobic interactions strengthen when warmed. The hSAFs are dual-peptide systems that only gel on mixing, which gives tight control over assembly. These properties raise possibilities for using the hSAFs as substrates in cell culture. We have tested this in comparison with the widely used Matrigel substrate, and demonstrate that, like Matrigel, hSAFs support both growth and differentiation of rat adrenal pheochromocytoma cells for sustained periods in culture.
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